Mianserin (1,2,3,4,10,14b-hexahydro-2-methyldibenzo [c,f]pyrazino[1,2-a]azepine) is a serotonin inhibitor and antihistamine compound whose preparation was disclosed in U.S. Pat. No. 3,534,041 to Organon. Derivatives of this compound are disclosed in British Patents No. 1498632 and 1498633.
Normianserin (Chemical Abstracts no. 71936-92-0), also known as desmethylmianserin, has similar pharmacological activity to that of mianserin but is less potent (Pinder, R. M. (1985) Acta Psychiatrica Scand. Act. 320 1-9; Doggrell, S. (1985) J. Pharm. Pharmacol. 37 116-20; Przegalinski, E., Rawlow, A., and Dohnal-Borak, 1. (1986) Polish J. Pharmacol. Pharm. 38 69-75).
A related class of dibenzo-pyrazino-azepines was disclosed in U.S. Pat. No. 3,701,778 (van der Burg). These compounds were stated to have anti-inflammatory, anti-serotonergic, anti-histamine and cardiovascular effects, while certain intermediates in their preparation were also pharmacologically active. The compounds included oxazepines, thiazepines and diazepines, and a variety of synthetic routes for obtaining the desired products was set forth.
It is known that many important pharmacological effects are mediated by 5-hydroxytryptamine, which is also known as serotonin. More recently, it has been established that receptors for 5-hydroxytryptamine are of five distinct sub-types, each having a characteristic pharmacological profile (reviewed by Fozard, J. R. (1987) Trends in Pharmacological Sciences 8 501-506). A variety of physical and mental conditions, such as migraine, depression, anxiety, and gastrointestinal disturbances, is susceptible to manipulation using agonists and antagonists of 5-hydroxytryptamine with binding activity at the different types of receptors. Mianserin, ketanserin, ritanserin and altanserin are all cited by Fozard (op. cit.) as being 5-HT.sub.2 -receptor antagonists.